The hypothesis that the pancreatic beta cell is a primary site of pathology in human and experimental diabetes, and the knowledge that the beta cell population is affected by genetic background and response to immunologic injury, has directed our attention to the need for further study of spontaneous animal models of Type l autoimmune diabetes. This request is for continued support of research projects designed to study the pathogenesis of diabetes in the unique model of insulin dependent diabetes, the Biobreeding/Worcester (BB/Wor) rat. The mechanism of Kilham rat virus (KRV) induced diabetes in BB/Wor diabetes resistant (DR) and other inbred rats will be studied using cellular immunology, molecular virology and immunocytochemistry. We will: * Test the hypothesis that KRV activates autoreactive effector cells. * Identify the phenotype of the diabetogenic effector cells. * Evaluate molecular mimicry as a model for diabetes induction. * Examine the role of beta-cell secretory activity in susceptibility to virus-induce diabetes. The research colony of BB/Wor rats will continue to be inbred and serve as the world's reference colony of this model of autoimmune diabetes. Virtually all of the proposed experiments are immunopathologic in nature. As such, they incorporate morphologic, cellular immunology, and molecular readout systems.